Oral vitamin C and endothelial function in smokers: short-term improvement, but no sustained beneficial effect

AbstractOBJECTIVESTo test the hypothesis that antioxidant therapy would improve endothelial function in smokers.BACKGROUNDSeveral studies have documented a beneficial effect of short-term oral or parenteral vitamin C on endothelial physiology in subjects with early arterial dysfunction. Possible long-term effects of vitamin C on endothelial function, however, are not known.METHODSWe studied the effects of short- and long-term oral vitamin C therapy on endothelial function in 20 healthy young adult smokers (age 36 ± 6 years, 8 male subjects, 21 ± 10 pack-years). Each subject was studied at baseline, 2 h after a single dose of 2 g vitamin C and 8 weeks after taking 1 g vitamin C daily, and after placebo, in a randomized double-blind crossover study. Blood samples were analyzed for plasma ascorbate levels and endothelial function was measured as flow-mediated dilation of the brachial artery, using high resolution ultrasound. Nitroglycerin-mediated dilation (endothelium-independent) was also measured at each visit.RESULTSAt baseline, plasma ascorbate level was low in the smokers (42 ± 21 μmol/liter; normal range, 50 to 150 μmol/liter), increased with vitamin C therapy after 2 h to 120 ± 54 μmol/liter (p < 0.001) and remained elevated after eight weeks of supplementation at 92 ± 32 μmol/liter (p < 0.001, compared with placebo). Flow-mediated dilation, however, increased at 2 h (from 2.8 ± 2.0% to 6.3 ± 2.8%, p < 0.001), but there was no sustained beneficial effect after eight weeks (3.9 ± 3.2%, p = 0.26). Nitroglycerin-mediated dilation was unchanged throughout.CONCLUSIONOral vitamin C therapy improves endothelial dysfunction in the short term in healthy young smokers, but it has no beneficial long-term effect, despite sustained elevation of plasma ascorbate levels

We Are All in This Together: The Role of Individuals’ Social Identities in Problematic Engagement with Video Games and the Internet

Individuals’ engagement with videogames and the internet features both social and potentially pathological aspects. In this research, we draw on the social identity approach and present a novel framework to understand the linkage between these two aspects. In three samples (Nstudy1 = 304, Nstudy2 = 160 and Nstudy3 = 782) of young Chinese people from two age groups (approximately 20 and 16 years old), we test the associations between relevant social identities and problematic engagement with videogames and the internet. Across studies, we demonstrate that individuals’ identification as ‘gamers’ or ‘frequent internet users’ predicts problematic engagement with videogames and the internet through stronger perceived social support from such groups. Moreover, we demonstrate that individuals’ identification as ‘students’ (Studies 2-3) is negatively associated with problematic engagement via social support from other students. Finally, in Study 3, we examine the articulation between social support from these three groups and subjective sense of loneliness. Findings indicate that, whereas perceived support from students is negatively associated with loneliness, the association between perceived support from gamers and internet users and loneliness is weaker and positive. Theoretical implications and directions for future research are discussed. Taken together, the studies highlight the importance of considering the social context of individuals’ problematic engagement with technologies, and the role of different group memberships

Within-Host Dynamics of Multi-Species Infections: Facilitation, Competition and Virulence

Host individuals are often infected with more than one parasite species (parasites defined broadly, to include viruses and bacteria). Yet, research in infection biology is dominated by studies on single-parasite infections. A focus on single-parasite infections is justified if the interactions among parasites are additive, however increasing evidence points to non-additive interactions being the norm. Here we review this evidence and theoretically explore the implications of non-additive interactions between co-infecting parasites. We use classic Lotka-Volterra two-species competition equations to investigate the within-host dynamical consequences of various mixes of competition and facilitation between a pair of co-infecting species. We then consider the implications of these dynamics for the virulence (damage to host) of co-infections and consequent evolution of parasite strategies of exploitation. We find that whereas one-way facilitation poses some increased virulence risk, reciprocal facilitation presents a qualitatively distinct destabilization of within-host dynamics and the greatest risk of severe disease

Female gamers’ experience of online harassment and social support in online gaming: a qualitative study

Female gaming is a relatively under-researched area, and female gamers often report experiencing harassment whilst playing online. The present study explored female experiences of social support while playing online video games, because of the previous research suggesting that females often experience harassment and negative interactions during game play. Data were collected from an online discussion forum, and comprised posts drawn from 271 female gamers. Thematic analysis of the discussions suggested that a lack of social support and harassment frequently led to female gamers playing alone, playing anonymously, and moving groups regularly. The female gamers reported experiencing anxiety and loneliness due to this lack of social support, and for many, this was mirrored in their experiences of social support outside of gaming. The female gamers frequently accepted the incorporation into their gaming of specific coping strategies to mitigate online harassment, including actively hiding their identity and avoiding all forms of verbal communication with other players. These themes are discussed in relation to relevant research in the area, along with recommendations for future research and consideration of possible explanations for the themes observed

Hypoxia and oxidative stress in breast cancer: Tumour hypoxia – therapeutic considerations

Conclusive research has shown that regions of acute/chronic hypoxia, which exist within the majority of solid tumours, have a profound influence on the therapeutic outcome of cancer chemotherapy and radiotherapy and are a strong prognostic factor of disease progression and survival. A strong argument therefore exists for assessing the hypoxic fraction of tumours, prior to patient treatment, and to tailor this treatment accordingly. Tumour hypoxia also provides a powerful physiological stimulus that can be exploited as a tumour-specific condition, allowing for the rationale design of hypoxia-activated anticancer drugs or novel hypoxia-regulated gene therapy strategies

Genetic identification of cytomegaloviruses in a rural population of Côte d'Ivoire.

BACKGROUND: Cytomegaloviruses (CMVs) are herpesviruses that infect many mammalian species, including humans. Infection generally passes undetected, but the virus can cause serious disease in individuals with impaired immune function. Human CMV (HCMV) is circulating with high seroprevalence (60-100 %) on all continents. However, little information is available on HCMV genoprevalence and genetic diversity in subsaharan Africa, especially in rural areas of West Africa that are at high risk of human-to-human HCMV transmission. In addition, there is a potential for zoonotic spillover of pathogens through bushmeat hunting and handling in these areas as shown for various retroviruses. Although HCMV and nonhuman CMVs are regarded as species-specific, potential human infection with CMVs of non-human primate (NHP) origin, shown to circulate in the local NHP population, has not been studied. FINDINGS: Analysis of 657 human oral swabs and fecal samples collected from 518 individuals living in 8 villages of Côte d'Ivoire with generic PCR for identification of human and NHP CMVs revealed shedding of HCMV in 2.5 % of the individuals. Determination of glycoprotein B sequences showed identity with strains Towne, AD169 and Toledo, respectively. NHP CMV sequences were not detected. CONCLUSIONS: HCMV is actively circulating in a proportion of the rural Côte d'Ivoire human population with circulating strains being closely related to those previously identified in non-African countries. The lack of NHP CMVs in human populations in an environment conducive to cross-species infection supports zoonotic transmission of CMVs to humans being at most a rare event

Physical activity but not sedentary activity is reduced in primary Sjögren’s syndrome

The aim of the study was to evaluate the levels of physical activity in individuals with primary Sjögren’s syndrome (PSS) and its relationship to the clinical features of PSS. To this cross-sectional study, self-reported levels of physical activity from 273 PSS patients were measured using the International Physical Activity Questionnaire-short form (IPAQ-SF) and were compared with healthy controls matched for age, sex and body mass index. Fatigue and other clinical aspects of PSS including disease status, dryness, daytime sleepiness, dysautonomia, anxiety and depression were assessed using validated tools. Individuals with PSS had significantly reduced levels of physical activity [median (interquartile range, IQR) 1572 (594–3158) versus 3708 (1732–8255) metabolic equivalent of task (MET) × min/week, p < 0.001], but similar levels of sedentary activity [median (IQR) min 300 (135–375) versus 343 (223–433) (MET) × min/week, p = 0.532] compared to healthy individuals. Differences in physical activity between PSS and controls increased at moderate [median (IQR) 0 (0–480) versus 1560 (570–3900) MET × min/week, p < 0.001] and vigorous intensities [median (IQR) 0 (0–480) versus 480 (0–1920) MET × min/week, p < 0.001]. Correlation analysis revealed a significant association between physical activity and fatigue, orthostatic intolerance, depressive symptoms and quality of life. Sedentary activity did not correlate with fatigue. Stepwise linear regression analysis identified symptoms of depression and daytime sleepiness as independent predictors of levels of physical activity. Physical activity is reduced in people with PSS and is associated with symptoms of depression and daytime sleepiness. Sedentary activity is not increased in PSS. Clinical care teams should explore the clinical utility of targeting low levels of physical activity in PSS

Multicentre cohort study to define and validate pathological assessment of response to neoadjuvant therapy in oesophagogastric adenocarcinoma

BACKGROUND: This multicentre cohort study sought to define a robust pathological indicator of clinically meaningful response to neoadjuvant chemotherapy in oesophageal adenocarcinoma. METHODS: A questionnaire was distributed to 11 UK upper gastrointestinal cancer centres to determine the use of assessment of response to neoadjuvant chemotherapy. Records of consecutive patients undergoing oesophagogastric resection at seven centres between January 2000 and December 2013 were reviewed. Pathological response to neoadjuvant chemotherapy was assessed using the Mandard Tumour Regression Grade (TRG) and lymph node downstaging. RESULTS: TRG (8 of 11 centres) was the most widely used system to assess response to neoadjuvant chemotherapy, but there was discordance on how it was used in practice. Of 1392 patients, 1293 had TRG assessment; data were available for clinical and pathological nodal status (cN and pN) in 981 patients, and TRG, cN and pN in 885. There was a significant difference in survival between responders (TRG 1–2; median overall survival (OS) not reached) and non-responders (TRG 3–5; median OS 2·22 (95 per cent c.i. 1·94 to 2·51) years; P < 0·001); the hazard ratio was 2·46 (95 per cent c.i. 1·22 to 4·95; P = 0·012). Among local non-responders, the presence of lymph node downstaging was associated with significantly improved OS compared with that of patients without lymph node downstaging (median OS not reached versus 1·92 (1·68 to 2·16) years; P < 0·001). CONCLUSION: A clinically meaningful local response to neoadjuvant chemotherapy was restricted to the small minority of patients (14·8 per cent) with TRG 1–2. Among local non-responders, a subset of patients (21·3 per cent) derived benefit from neoadjuvant chemotherapy by lymph node downstaging and their survival mirrored that of local responders

Moralizing biology: the appeal and limits of the new compassionate view of nature

In recent years, a proliferation of books about empathy, cooperation and pro-social behaviors (Brooks, 2011a) has significantly influenced the discourse of the life-sciences and reversed consolidated views of nature as a place only for competition and aggression. In this article I describe the recent contribution of three disciplines – moral psychology (Jonathan Haidt), primatology (Frans de Waal) and the neuroscience of morality – to the present transformation of biology and evolution into direct sources of moral phenomena, a process here named the ‘moralization of biology’. I conclude by addressing the ambivalent status of this constellation of authors, for whom today ‘morality comes naturally’: I explore both the attractiveness of their message, and the problematic epistemological assumptions of their research-programs in the light of new discoveries in developmental and molecular biology

Imaging biomarker roadmap for cancer studies.

Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing 'translational gaps' through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored 'roadmap'. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use.Development of this roadmap received support from Cancer Research UK and the Engineering and Physical Sciences Research Council (grant references A/15267, A/16463, A/16464, A/16465, A/16466 and A/18097), the EORTC Cancer Research Fund, and the Innovative Medicines Initiative Joint Undertaking (grant agreement number 115151), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies' in kind contribution